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Mitochondrial RNA polymerase (mtRNAP) is crucial in cellular energy production, yet understanding of mitochondrial DNA transcription initiation lags that of bacterial and nuclear DNA transcription. We report structures of two transcription initiation intermediate states of yeast mtRNAP that explain promoter melting, template alignment, DNA scrunching, abortive synthesis, and transition into elongation. In the partially melted initiation complex (PmIC), transcription factor MTF1 makes base-specific interactions with flipped non-template (NT) nucleotides "AAGT" at -4 to -1 positions of the DNA promoter. In the initiation complex (IC), the template in the expanded 7-mer bubble positions the RNA and NTP analog UTPαS, while NT scrunches into an NT loop. The scrunched NT loop is stabilized by the centrally positioned MTF1 C-tail. The IC and PmIC states coexist in solution, revealing a dynamic equilibrium between two functional states. Frequent scrunching/unscruching transitions and the imminent steric clashes of the inflating NT loop and growing RNA:DNA with the C-tail explain abortive synthesis and transition into elongation.
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DNA Mitocondrial/genética , RNA Polimerases Dirigidas por DNA/genética , Mitocôndrias/genética , Proteínas Mitocondriais/genética , RNA Mitocondrial/genética , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Fatores de Transcrição/genética , Sítios de Ligação , Microscopia Crioeletrônica , DNA Mitocondrial/química , DNA Mitocondrial/metabolismo , RNA Polimerases Dirigidas por DNA/química , RNA Polimerases Dirigidas por DNA/metabolismo , Mitocôndrias/metabolismo , Proteínas Mitocondriais/química , Proteínas Mitocondriais/metabolismo , Modelos Moleculares , Motivos de Nucleotídeos , Regiões Promotoras Genéticas , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , RNA Mitocondrial/química , RNA Mitocondrial/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/metabolismo , Termodinâmica , Elongação da Transcrição Genética , Fatores de Transcrição/química , Fatores de Transcrição/metabolismo , Iniciação da Transcrição GenéticaRESUMO
Understanding the dynamics of biomolecules in complex environments is crucial for elucidating the effect of condensed and heterogeneous environments on their functional properties. A relevant environment-and one that can also be mimicked easily in vitro-is that of phase-separated droplets. While phase-separated droplet systems have been shown to compartmentalize a wide range of functional biomolecules, the effects of internal structuration of droplets on the dynamics and mobility of internalized molecules remain poorly understood. Here, we use fluorescence correlation spectroscopy to measure the dynamics of short oligonucleotides encapsulated within two representative kinds of uncharged and charged phase-separated droplets. We find that the internal structuration controls the oligonucleotide dynamics in these droplets, revealed by measuring physical parameters at high spatiotemporal resolution. By varying oligonucleotide length and salt concentrations (and thereby charge screening), we found that the dynamics are significantly affected in the noncharged droplets compared to the charged system. Our work lays the foundation for unraveling and quantifying the physical parameters governing biomolecular transport in the condensed environment.
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DNA , DNA/química , Oligonucleotídeos/química , Espectrometria de Fluorescência , Oligodesoxirribonucleotídeos/químicaRESUMO
Twinkle is the ring-shaped replicative helicase within the human mitochondria with high homology to bacteriophage T7 gp4 helicase-primase. Unlike many orthologs of Twinkle, the N-terminal domain (NTD) of human Twinkle has lost its primase activity through evolutionarily acquired mutations. The NTD has no demonstrated activity thus far; its role has remained unclear. Here, we biochemically characterize the isolated NTD and C-terminal domain (CTD) with linker to decipher their contributions to full-length Twinkle activities. This novel CTD construct hydrolyzes ATP, has weak DNA unwinding activity, and assists DNA polymerase γ (Polγ)-catalyzed strand-displacement synthesis on short replication forks. However, CTD fails to promote multikilobase length product formation by Polγ in rolling-circle DNA synthesis. Thus, CTD retains all the motor functions but struggles to implement them for processive translocation. We show that NTD has DNA-binding activity, and its presence stabilizes Twinkle oligomerization. CTD oligomerizes on its own, but the loss of NTD results in heterogeneously sized oligomeric species. The CTD also exhibits weaker and salt-sensitive DNA binding compared with full-length Twinkle. Based on these results, we propose that NTD directly contributes to DNA binding and holds the DNA in place behind the central channel of the CTD like a "doorstop," preventing helicase slippages and sustaining processive unwinding. Consistent with this model, mitochondrial single-stranded DNA-binding protein (mtSSB) compensate for the NTD loss and partially restore kilobase length DNA synthesis by CTD and Polγ. The implications of our studies are foundational for understanding the mechanisms of disease-causing Twinkle mutants that lie in the NTD.
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DNA Helicases , Proteínas Mitocondriais , Humanos , DNA/metabolismo , DNA Helicases/metabolismo , DNA Primase/genética , DNA Primase/metabolismo , Replicação do DNA , DNA Mitocondrial/metabolismo , Mitocôndrias/genética , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismoRESUMO
The proofreading exonuclease activity of replicative DNA polymerase excises misincorporated nucleotides during DNA synthesis, but these events are rare. Therefore, we were surprised to find that T7 replisome excised nearly 7% of correctly incorporated nucleotides during leading and lagging strand syntheses. Similar observations with two other DNA polymerases establish its generality. We show that excessive excision of correctly incorporated nucleotides is not due to events such as processive degradation of nascent DNA or spontaneous partitioning of primer-end to the exonuclease site as a "cost of proofreading". Instead, we show that replication hurdles, including secondary structures in template, slowed helicase, or uncoupled helicase-polymerase, increase DNA reannealing and polymerase backtracking, and generate frayed primer-ends that are shuttled to the exonuclease site and excised efficiently. Our studies indicate that active-site shuttling occurs at a high frequency, and we propose that it serves as a proofreading mechanism to protect primer-ends from mutagenic extensions.
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Bacteriófago T7/genética , DNA Primase/metabolismo , Reparo do DNA/genética , Replicação do DNA/genética , DNA Polimerase Dirigida por DNA/metabolismo , DNA/biossíntese , Bacteriófago T7/enzimologia , Domínio Catalítico , DNA Primase/genética , Primers do DNA/genética , DNA Polimerase Dirigida por DNA/genética , Exodesoxirribonucleases/genética , Exodesoxirribonucleases/metabolismo , Mutação , Nucleotídeos/genéticaRESUMO
INTRODUCTION: Successful biliary drainage and antibiotics are the mainstays of therapy in management of patients with acute cholangitis. However, the duration of antibiotic therapy after successful biliary drainage has not been prospectively evaluated. We conducted a single-center, randomized, noninferiority trial to compare short duration of antibiotic therapy with conventional duration of antibiotic therapy in patients with moderate or severe cholangitis. METHODS: Consecutive patients were screened for the inclusion criteria and randomized into either conventional duration (CD) group (8 days) or short duration (SD) group (4 days) of antibiotic therapy. The primary outcome was clinical cure (absence of recurrence of cholangitis at day 30 and >50% reduction of bilirubin at day 15). Secondary outcomes were total days of antibiotic therapy and hospitalization within 30 days, antibiotic-related adverse events, and all-cause mortality at day 30. RESULTS: The study included 120 patients (the mean age was 55.85 ± 13.52 years, and 50% were male patients). Of them, 51.7% patients had malignant etiology and 76.7% patients had moderate cholangitis. Clinical cure was seen in 79.66% (95% confidence interval, 67.58%-88.12%) patients in the CD group and 77.97% (95% confidence interval, 65.74%-86.78%) patients in the SD group ( P = 0.822). On multivariate analysis, malignant etiology and hypotension at presentation were associated with lower clinical cure. Total duration of antibiotics required postintervention was lower in the SD group (8.58 ± 1.92 and 4.75 ± 2.32 days; P < 0.001). Duration of hospitalization and mortality were similar in both the groups. DISCUSSION: Short duration of antibiotics is noninferior to conventional duration in patients with moderate-to-severe cholangitis in terms of clinical cure, recurrence of cholangitis, and overall mortality.
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Antibacterianos , Colangite , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Feminino , Doença Aguda , Colangite/tratamento farmacológico , Colangite/etiologiaRESUMO
The upper eyelid is a complex structural part of the face that plays an important role in protecting the cornea from drying and damage to preserve vision. The eyelashes are an essential part of the upper eyelid and help in protecting the eyes from dust, foreign bodies, and sweat. Being a part of the face, which is the most noticeable part of the body, both structures hold an important role in reconstructive procedures. Reconstruction of both structures simultaneously is tricky but helps reduce the number of procedures required in achieving an aesthetically acceptable eye. Our techniques describe the use of the paramedian forehead flap with an anterior hairline to reconstruct the upper eyelid and eyelashes in a single stage in a posttraumatic near-total upper eyelid defect with a favorable outcome. Depending on the parting of the patient's hair, the anterior hairline of one side can be included in the distal edge of the flap while raising, which can be inset so that the direction and orientation of the eyelashes perfectly match. Our technique refurbishes an established technique for eyelid reconstruction to include eyelash reconstruction at the same time, thus saving time and resources without any inconvenience to the patient.
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Strand exchange between homologous nucleic acid sequences is the basis for cellular DNA repair, recombination, and genome editing technologies. Specialized enzymes catalyze cellular strand exchange; however, the reaction occurs spontaneously when a single-stranded DNA toehold can dock the invader strand on the target DNA to initiate strand exchange through branch migration. Due to its precise response, the spontaneous toehold-mediated strand displacement (TMSD) reaction is widely employed in DNA nanotechnology. However, enzyme-free TMSD suffers from slow rates, resulting in slow response times. Here, we show that human mitochondrial DNA helicase Twinkle can accelerate TMSD up to 6000-fold. Mechanistic studies indicate that Twinkle accelerates TMSD by catalyzing the docking step, which typically limits spontaneous reactions. The catalysis occurs without ATP, and Twinkle-catalyzed TMSD rates remain sensitive to base-pair mismatches. The simple catalysis, tunability, and speed improvement of the catalyzed TMSD can be leveraged in nanotechnology, requiring sensitive detection and faster response times.
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BACKGROUND: Ulcerative colitis is a relapsing and remitting disease that may be associated with flares. The causes of flares in the Indian setting are not well recognized. METHODS: The present prospective case-control study was conducted at a single center in North India. Cases were defined as patients admitted for flare of ulcerative colitis, while controls were patients in remission enrolled from the outpatient department. The basis of the diagnosis of flare was a simple clinical colitis activity index (SCCAI) of ≥ 5 and endoscopic activity, while remission was based on SCCAI < 4 and a normal fecal calprotectin. A questionnaire evaluating recent infections, stress, drug intake (antibiotics, pain medication), adherence to therapy, and use of complementary and alternative therapy (CAM) was administered. RESULTS: We included 84 patients (51 with flare and 33 in remission) with a median age of 38 years, of whom 47 (55.9%) were males. The two groups were similar for baseline parameters, including age (38, 23-50 and 38, 25.5-48.5 years), male gender (52.9% and 60.6%), extent of disease, extraintestinal manifestations (21.6% and 12.1%), use of 5-aminosalicylates (76.5% and 90.9%). The thiopurine use was lower in those having a flare (15.7% and 36.4%). Amongst the predictors of flare, the recent infections (39.2% and 30.3%), recent travel (31.4 and 27.3%), eating outside food (47.1% and 39.4%), consumption of milk products (88.2% and 75.8%), use of pain medication (43.1% and 33.3%) and recent stress (62.7% and 60.6%) were similar between cases and controls. The rates of antibiotic use (29.4% and 6.1%), lack of adherence (50.9% and 15.2%), and intake of CAM (70.6% and 33.3%) were higher in those with flare. Patients attributed a lack of adherence to the cost of therapy, presumed cure (due to lack of symptoms), and fear of adverse effects. CONCLUSION: Lack of adherence to inflammatory bowel disease therapies and recent CAM and antibiotic intake was higher in patients with flares of UC. The study makes ground for educational intervention(s) promoting knowledge and adherence to IBD therapies.
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Colite Ulcerativa , Colite , Doenças Inflamatórias Intestinais , Humanos , Masculino , Adulto , Feminino , Colite Ulcerativa/tratamento farmacológico , Estudos de Casos e Controles , Doenças Inflamatórias Intestinais/tratamento farmacológico , Mesalamina/uso terapêutico , Antibacterianos/uso terapêutico , Colite/tratamento farmacológicoRESUMO
With national interest in seaweed-based biofuels as a sustainable alternative to fossil fuels, there is a need for tools that produce high-yield seaweed cultivars and increase the efficiency of offshore farms. Several agricultural studies have demonstrated that the application of microbial inoculants at an early life stage can improve crop yield, and there is an opportunity to use similar techniques in seaweed aquaculture. However, there is a critical knowledge gap regarding host-microbiome associations of macroalgae gametophytes in germplasm cultures. Here, we investigate the microbial community of Macrocystis pyrifera gametophyte germplasm cultures that were used to cultivate an offshore farm in Santa Barbara, California and identify key taxa correlated with increased biomass of mature sporophytes. This work provides a valuable knowledge base for the development of microbial inoculants that produce high-biomass M. pyrifera cultivars to ultimately be used as biofuel feedstocks.
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Macrocystis , Alga Marinha , Células Germinativas Vegetais , BiomassaRESUMO
INTRODUCTION: Endoscopic dilation is the preferred management strategy for caustic esophageal strictures (CES). However, the differences in outcome for different dilators are not clear. We compared the outcome of CES using bougie and balloon dilators. METHODS: Between January 2000 and December 2016, the following data of all the patients with CES were collected: demographic parameters, substance ingestion, number of strictures, number of dilations required to achieve ≥ 14 mm dilation, post-dilation recurrence, and total dilations. Patients were divided into two groups for the type of dilator, i.e., bougie or balloon. The two groups were compared for baseline parameter, technical success, short- and long-term clinical success, refractory strictures, recurrence rates, and major complications. RESULTS: Of the 189 patients (mean age 32.17 ± 12.12 years) studied, 119 (62.9%) were males. 122 (64.5%) patients underwent bougie dilation and 67 (35.5%) received balloon dilation. Technical success (90.1% vs. 68.7%, p < 0.001), short-term clinical success (65.6% vs. 46.3%, p value 0.01), and long-term clinical success (86.9% vs. 64.2%, p < 0.01) were higher for bougie dilators compared to balloon dilators. Twenty-four (12.7%) patients developed adverse events which were similar for two groups. On multivariate analysis, use of bougie dilators (aOR 4.868, 95% CI 1.027-23.079), short-term clinical success (aOR 5.785, 95% CI 1.203-27.825), and refractory strictures (aOR 0.151, 95% CI 0.033-0.690) were independent predictors of long-term clinical success. CONCLUSION: Use of bougie dilators is associated with better clinical success in patients with CES compared to balloon dilators with similar rates of adverse events.
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Cáusticos , Estenose Esofágica , Masculino , Humanos , Adulto Jovem , Adulto , Feminino , Estenose Esofágica/induzido quimicamente , Estenose Esofágica/terapia , Cáusticos/toxicidade , Dilatação , Constrição Patológica/etiologia , Centros de Atenção Terciária , Estudos Retrospectivos , Resultado do Tratamento , Esofagoscopia/efeitos adversosRESUMO
BACKGROUND: Incidence and risk factors for the development of extremity deep vein thrombosis (eDVT) in admitted patients of acute pancreatitis have been rarely explored. AIMS: To identify the incidence of eDVT and to explore role of clinical scores for predicting eDVT in admitted patients of acute pancreatitis. METHODS: We prospectively enrolled admitted patients of acute pancreatitis and performed a weekly eDVT screen for the duration of their admission. Well's score and Padua's score were also calculated weekly. The incidence of venous thrombosis (eDVT and splanchnic thrombosis based on contrast-enhanced CT scan abdomen) was noted, and the risk factors were determined using multivariate analysis. The correlation between Well's score, Padua's score, and development of DVT was calculated using Pearson's correlation. RESULTS: Of the 102 patients of acute pancreatitis enrolled, 73.5% of patients had necrotizing pancreatitis. Total of 46 patients (45.1%) developed thrombosis: 43 patients had splanchnic vein thrombosis; 5 patients had eDVT; and 1 patient had pulmonary embolism. Patients with eDVT had higher BISAP score (2.6 ± 0.9 vs 1.7 ± 0.8; p = 0.039), requirement of mechanical ventilation (60% vs 8.2%; p = 0.008), and mortality (60% vs 12.4%; p = 0.022). Well's score of ≥ 2 had sensitivity and specificity of 80% and 96.9% for prediction of eDVT and it had better correlation with the development of eDVT compared to Pauda's score. CONCLUSION: Incidence of DVT is 5% in patients with acute pancreatitis requiring admission. It is associated with higher disease severity and mortality. The Well's score is useful to predict the development of eDVT in routine clinical practice.
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Pancreatite , Trombose , Trombose Venosa , Humanos , Pancreatite/complicações , Pancreatite/epidemiologia , Estudos Prospectivos , Doença Aguda , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/epidemiologia , Trombose Venosa/complicaçõesRESUMO
The corticosteroids have been used for preemptive management of surgical sequelae after mandibular third molar extraction. The aim of this article was to review the efficacy of methylprednisolone versus dexamethasone in the management of postsurgical pain, swelling, and trismus after mandibular third molar surgery. Randomized, double-blinded studies from PubMed, CINAHL, Scopus, DOSS, Cochrane central, and Web of Science were identified by using a search strategy. Randomized controlled trials evaluating the efficacy of use of dexamethasone versus methylprednisolone for mandibular third molar extraction were only considered. The studies involving the use of any other corticosteroid agent were excluded. Outcomes assessed were postoperative pain, the number of rescue analgesics required, swelling, trismus, and adverse events. The search strategy yielded 1046 articles for title and abstract screening, out of which only seven studies were included in the systematic review after full text screening. There was considerable heterogeneity between the studies with regards to the method as well as the parameters assessed. Risk of bias was low in three studies and unclear in other four studies. On pooled analyses, there was no significant difference with respect to pain, rescue analgesics, and swelling in the test and the control group. Forest plot analysis showed that dexamethasone had lesser trismus in early postoperative period (postoperative day 2) as compared to methylprednisolone. None of the included studies reported any adverse effects. Both the corticosteroids have similar efficacy in reducing the postoperative pain and swelling; however, dexamethasone showed statistically significant difference from methylprednisolone in reducing trismus (estimated standardized mean difference of -0.69 mm; 95% CI: -1.01 to -0.38; p < 0.0001) in the early postoperative period. However, due to statistical heterogeneity, quality of the evidence for the review was low to moderate. Hence, more studies with larger study sample and low risk of bias are needed to confirm these results.
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Metilprednisolona , Dente Impactado , Humanos , Metilprednisolona/uso terapêutico , Dexametasona/uso terapêutico , Dente Serotino/cirurgia , Trismo/tratamento farmacológico , Trismo/etiologia , Trismo/prevenção & controle , Corticosteroides , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controle , Edema , Extração Dentária/efeitos adversos , Extração Dentária/métodos , Dente Impactado/cirurgiaRESUMO
BACKGROUND AND AIMS: The serological responses after severe acute respiratory syndrome coronavirus 2 vaccination may be attenuated in immunocompromised individuals. The study aimed to systematically evaluate the seroconversion rates after complete vaccination for coronavirus disease 2019 (COVID-19) in patients with inflammatory bowel disease (IBD). METHODS: Electronic databases were searched to identify studies reporting response to COVID-19 vaccination in IBD. Pooled seroconversion rates after complete vaccination were calculated. Subgroup analysis for vaccine types was also performed. Pooled seroconversion rates for various drugs or classes were also estimated. The pooled rates of breakthrough infections in vaccinated IBD patients were estimated. The pooled neutralization rates after complete vaccination were also estimated. The studies reporting durability of titers were systematically assessed. RESULTS: A total of 46 studies were included. The pooled seroconversion rate for complete vaccination (31 studies, 9447 patients) was 0.96 (95% confidence interval [CI], 0.94-0.97; I2 = 90%). When compared with healthy control subjects, the pooled relative risk of seroconversion was lower (0.98; 95% CI, 0.98-0.99; I2 = 39%). The pooled seroconversion rates were statistically similar among various drug classes. The pooled positivity of neutralization assays (8 studies, 771 participants) was 0.80 (95% CI, 0.70-0.87; I2 = 82%). The pooled relative risk of breakthrough infections in vaccinated IBD patients was similar to vaccinated control subjects (0.60; 95% CI, 0.25-1.42; I2 = 79%). Most studies suggested that titers fall after 4 weeks of COVID-19 vaccination, and the decay was higher in patients on anti-tumor necrosis factor alone or combination with immunomodulators. An additional dose of COVID-19 vaccine elicited serological response in most nonresponders to complete vaccination. CONCLUSIONS: Complete COVID-19 vaccination is associated with seroconversion in most patients with IBD. The decay in titers over time necessitates consideration of additional doses in these patients.
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COVID-19 , Doenças Inflamatórias Intestinais , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Humanos , Hospedeiro Imunocomprometido , Doenças Inflamatórias Intestinais/complicações , VacinaçãoRESUMO
BACKGROUND: The prevalence of AP in pregnancy (APIP) is uncertain with varying reports of its impact on maternal and foetal outcomes. OBJECTIVES: This study was aimed to find the prevalence of APIP and its effect on the maternal and foetal outcomes. SEARCH STRATEGY: Electronic databases were searched upto 31.05.2020 for the appropriate studies. SELECTION CRITERIA: Prospective, retrospective observational studies or case series evaluating APIP in terms of maternal and foetal outcomes were included. DATA COLLECTION AND ANALYSIS: Data on the prevalence of APIP, etiology, maternal mortality rates and foetal outcomes were collated. Due to high heterogeneity among the studies, the data has been represented as a systematic review. RESULTS: A total of 16 studies with 8466 pregnant patients were included in the systematic review. The overall prevalence of APIP ranged from 0.225/1000 pregnancies to 2.237/1000 pregnancies. Gallstone disease was the most common cause ranging from 14.29 to 96.3%, with eastern studies reporting more cases of hypertriglyceridemia as etiology. Mild pancreatitis was noted in 33.33-100% of cases with milder disease among western studies. APIP incidence was higher during 3rd trimester (27.27%-95.24%). Maternal mortality ranged from 0 to 12.12/100 pregnancies. Foetal loss ranged from 0 to 23.08%, with adverse foetal outcomes ranging from 0 to 57.41%. Neonatal mortality ranged from 0 to 75.5/1000 neonatal live birth. CONCLUSION: APIP is usually mild, but its incidence increases with gestational age. Maternal outcome is usually good but adverse foetal outcome is high in APIP (PROSPERO No.: CRD42020194313).
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Pancreatite , Complicações na Gravidez , Doença Aguda , Feminino , Humanos , Recém-Nascido , Pancreatite/epidemiologia , Pancreatite/etiologia , Gravidez , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/etiologia , Estudos Prospectivos , Estudos RetrospectivosRESUMO
The use of colloid supported lipid bilayers (CSLBs) for assembling colloidal structures has been of recent interest. Here, we use multi-component lipid bilayer membranes formed around anisotropic colloids and show that the curvature anisotropy of the colloids drives a sorting of the lipids in the membrane along the colloids. We then exploit this curvature-sensitive lipid sorting to create "shape-anisotropic patchy colloids" - specifically, we use colloids with six rods sticking out of a central cubic core, "hexapods", for this purpose and demonstrate that membrane patches self-assemble at the tip of each of the six colloidal rods. The membrane patches are rendered sticky using biotinylated lipids in complement with a biotin-binding streptavidin protein. Finally, using these "shape-anisotropic patchy colloids", we demonstrate the directed assembly of colloidal links, paving the way for the creation of heterogeneous and flexible colloidal structures.
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Coloides , Bicamadas Lipídicas , Anisotropia , Coloides/química , Bicamadas Lipídicas/química , Transporte ProteicoRESUMO
An elegant and catalytic procedure for the one-step cyanomethylenation of C(sp3)-H bonds adjacent to benzazoles and ketones is described herein using DMF as a C-1 unit and TMSCN as the cyanide source. The copper-mediated reaction between DMF and TMSCN gives a cyanomethylene radical intermediate that reacts with 2-alkylbenzazoles or alkylketones to furnish desired cyanomethylenated compounds under palladium catalysis. Subsequent interconversion of cyanomethylenated products makes the protocol synthetically attractive.
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In general, the α-functionalization of carboxylic acid derivatives requires either a transition metal catalyst or a stoichiometric activating agent/strong base/external additive. A transition metal free α-chalcogenation of aliphatic carboxylic acid equivalents is reported herein via ion pair formation using K3PO4 as a catalyst. Mild conditions, broad scope, scalability of the process, attaining bioactive glucokinase activators, and some synthetic intermediates establish merits of the strategy.
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Ácidos Graxos , Elementos de Transição , Ácidos Carboxílicos , Catálise , Elementos de Transição/químicaRESUMO
Background & objectives: Coronavirus disease 2019 (COVID-19) affects respiratory, gastrointestinal, cardiovascular and other systems disease. Studies describing liver involvement and liver function test (LFT) abnormalities are sparse from our population. This study was undertaken to estimate the LFT abnormalities in patients with COVID-19 in a tertiary care set up in India. Methods: In this retrospective study conducted at a tertiary care centre in Mumbai, India, all consecutive patients with proven COVID-19 by reverse transcriptase-PCR from March 23 to October 31, 2020 were enrolled. Of the 3280 case records profiled, 1474 cases were included in the study. Clinical characteristics, biochemical parameters and outcomes were recorded. Results: Overall 681 (46%) patient had deranged LFTs. Hepatocellular type of injury was most common (93%). Patients with deranged LFTs had more probability of developing severe disease (P<0.001) and mortality (P<0.001). Advanced age (P<0.001), male gender (P<0.001), diabetes mellitus (P<0.001), lower oxygen saturation levels at admission (P<0.001), higher neutrophil-lymphocyte ratio (P<0.001), history of diabetes mellitus and cirrhosiss were associated with deranged LFTs. Acute liver injury was seen in 65 (4.3%) cases on admission and 57 (3.5%) cases during hospital stay. On multivariate analysis for predicting mortality, age >60 yr serum creatinine >2 mg%, PaO2/FiO2 ratio ≤200 and raised AST >50 IU/l (OR: 2.34, CI: 1.59-3.48, P<0.001) were found to be significant. Interpretation & conclusions: In COVID-19, LFT abnormalities were common, and derangement increased as severity progressed. The presence of deranged LFT worsens the clinical outcome and predicts in-hospital mortality.
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COVID-19 , Humanos , Masculino , Testes de Função Hepática , SARS-CoV-2 , Centros de Atenção Terciária , Estudos RetrospectivosRESUMO
BACKGROUND: Sunflower is an important oilseed crop domesticated in North America approximately 4000 years ago. During the last century, oil content in sunflower was under strong selection. Further improvement of oil properties achieved by modulating its fatty acid composition is one of the main directions in modern oilseed crop breeding. RESULTS: We searched for the genetic basis of fatty acid content variation by genotyping 601 inbred sunflower lines and assessing their lipid and fatty acid composition. Our genome-wide association analysis based on the genotypes for 15,483 SNPs and the concentrations of 23 fatty acids, including minor fatty acids, revealed significant genetic associations for eleven of them. Identified genomic regions included the loci involved in rare fatty acids variation on chromosomes 3 and 14, explaining up to 34.5% of the total variation of docosanoic acid (22:0) in sunflower oil. CONCLUSIONS: This is the first large scale implementation of high-throughput lipidomic profiling to sunflower germplasm characterization. This study contributes to the genetic characterization of Russian sunflower collections, which made a substantial contribution to the development of sunflower as the oilseed crop worldwide, and provides new insights into the genetic control of oil composition that can be implemented in future studies.
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Ácidos Graxos/análise , Helianthus , Óleos de Plantas/análise , Estudos de Associação Genética , Genótipo , Helianthus/genética , América do Norte , Melhoramento Vegetal , Federação RussaRESUMO
OBJECTIVE: Acute pancreatitis (AP) is a common disorder with high mortality in severe cases. Several markers have been studied to predict development of severe AP (SAP) including serum resistin with conflicting results. This study aimed at assessing the role of baseline serum resistin levels in predicting SAP. METHODS: This prospective study collected data from 130 AP patients from July 2017 to Nov 2018. Parameters measured included demographic profile, serum resistin at admission, severity scores, hospital stay, surgery, and mortality. Patients were divided into two groups, severe and non-severe AP. The two groups were compared for baseline characteristics, serum resistin levels, hospital stay, surgery and mortality. RESULTS: Among 130 patients, 53 patients had SAP. SAP patients had higher BMI, baseline CRP, APACHE II and CTSI scores (p-value 0.045, <0.001, <0.001 and 0.001, respectively). Both groups had comparable serum resistin levels. Serum resistin levels were also not different for obese and non-obese patients (p-value = 0.62). On multivariate analysis, BMI and high APACHE II score and CRP levels were found to independently predict SAP. CONCLUSION: We found that serum resistin is not a useful marker for predicting the severity of AP and does not correlate with increasing body weight.